Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada; Laboratory of Self-Organizing Soft Matter, Eindhoven University of Technology PO Box 513, 5600 MB Eindhoven, the Netherlands; Laboratory of Chemical Biology, Eindhoven University of Technology PO Box 513, 5600 MB Eindhoven, the Netherlands; Institute for Complex Molecular Systems, Eindhoven University of Technology PO Box 513, 5600 MB Eindhoven, the Netherlands.
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada.
Cell Rep. 2021 Nov 16;37(7):110002. doi: 10.1016/j.celrep.2021.110002.
Infections typically begin with pathogens adhering to host cells. For bacteria, this adhesion can occur through specific ligand-binding domains. We identify a 20-kDa peptide-binding domain (PBD) in a 1.5-MDa RTX adhesin of a Gram-negative marine bacterium that colonizes diatoms. The crystal structure of this Ca-dependent PBD suggests that it may bind the C termini of host cell-surface proteins. A systematic peptide library analysis reveals an optimal tripeptide sequence with 30-nM affinity for the PBD, and X-ray crystallography details its peptide-protein interactions. Binding of the PBD to the diatom partner of the bacteria can be inhibited or competed away by the peptide, providing a molecular basis for inhibiting bacterium-host interactions. We further show that this PBD is found in other bacteria, including human pathogens such as Vibrio cholerae and Aeromonas veronii. Here, we produce the PBD ortholog from A. veronii and demonstrate, using the same peptide inhibitor, how pathogens may be prevented from adhering to their hosts.
感染通常始于病原体附着在宿主细胞上。对于细菌，这种附着可以通过特定的配体结合结构域来实现。我们在一种定植于硅藻的革兰氏阴性海洋细菌的 1.5 MDa RTX 黏附素中鉴定出一个 20 kDa 的肽结合结构域 (PBD)。该 Ca 依赖性 PBD 的晶体结构表明，它可能结合宿主细胞表面蛋白的 C 末端。系统的肽文库分析揭示了一个最佳的三肽序列，其对 PBD 的亲和力为 30 nM，X 射线晶体学详细描述了其肽-蛋白相互作用。该 PBD 与细菌的硅藻伙伴的结合可以被肽抑制或竞争，为抑制细菌-宿主相互作用提供了分子基础。我们进一步表明，这种 PBD 存在于其他细菌中，包括人类病原体如霍乱弧菌和维氏气单胞菌。在这里，我们从 A. veronii 中产生了 PBD 同源物，并使用相同的肽抑制剂证明了病原体如何被阻止附着在它们的宿主上。
